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Division of Nuclear Medicine, Department of Radiology,

Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand

6th International Conference on Biomarkers & Clinical Research

Surasawadee Ausavarat Ph.D.

Efficacy of TSHR mRNA

in the follow-up of

differentiated thyroid cancer

Outline Presentation

• Thyroglobulin (Tg) as a tumor marker of DTC

• Thyroid-specific mRNA as a surrogate or adjunctive marker

• Efficacy of TSHR mRNA in the follow-up of DTC

• Further studies

Thyroglobulin

Thyroglobulin

• Thyroglobulin levels in the blood are mainly used as a tumor

marker for differentiated thyroid carcinoma.

• Following thyroidectomy and radioactive iodine ablation

thyroglobulin levels can be serially monitored.

• A subsequent elevation of the thyroglobulin levels is an

indication of recurrence or metastatic disease.

Limitations of Serum Thyroglobulin

• Endogenous anti-thyroglobulin

antibodies (TgAb) can interfere with

thyroglobulin measurement.

• 15–25% of patients with DTC are

TgAb-positive

• Low sensitivity during thyroid

hormone suppression therapy

• Different methods of detection:

• RIA / IMAs / ECLIA

Detection of Thyroid-specific mRNA

Quantitative

Ag-Ab interaction detection

Quantitative

Molecular detection

Qualitative

Molecular detection

Picture from URL: http://genius.com/Biology-genius-the-central-dogma-annotated

Detection of Thyroid-specific mRNA

Picture from Gutnick J, Soldes O, Gupta M, Milas M. Circulating thyrotropin receptor messenger RNA for evaluation of thyroid nodules and

surveillance of thyroid cancer in children.J Pediatr Surg. 2012 Jan;47(1):171-6.

Thyroid Cancer Cells

• No interference of TgAb by molecular method

• High sensitivity during thyroid hormone therapy

• Identify postoperative patients at risk for

metastatic thyroid cancer

Example of Thyroid-specific mRNA

• Thyroglobulin (Tg)

• Thyroid stimulating hormone receptor (TSHR)

• Thyroid peroxidase (TPO)

• Sodium/iodide symporter (NIS)

Review of Tg mRNA

ATA Guidelines 2009

• Tg mRNA may be a sensitive marker for persistent thyroid cells

• RNA extraction is not well standardized

• Question about its specificity

• Future studies optimizing the measurement are needed

TSH-receptor mRNA

Objectives

• Evaluate the efficacy of TSHR mRNA in the follow-up of DTC

• Efficacy of TSHR mRNA in TgAb-positive patients

• Comparative study of serum Tg, TSHR mRNA and total body

scan

Materials and Methods

n=160

DTC patients

n=49

NED

n=14

Thyroid remnants

n=28

Biochemical

persistent disease

n=69

Structural persistent

disease

n=25

Locoregional

disease

n=44

Distant metastasis

n=27

Control subjects

Materials and Methods

Results

Results

Results

Conclusions

• TSHR mRNA seems to be highly sensitive in TgAb-positive

patients only.

• 24 out of 27 TgAb+ve patients were positive for either TSHR

mRNA with sensitivity 88.2% of and specificity of 42.9%.

• 2 patients with distant metastasis who were positive for TSHR

mRNA had undetectable serum Tg (<0.1 ng/mL) and higher

than the upper limit of TgAb (>4,000 IU/mL).

Conclusions

• This emphasizes that serum Tg remains the most efficient

marker for thyroid carcinoma management.

• TSHR mRNA assay depends on molecular technique which is

much more expensive and time-consuming.

• Second generation of Tg assay made it possible to be sensitive

enough for detecting basal Tg without TSH stimulation.

• TSHR mRNA assay may be used as an adjunctive marker in

patients whose serum Tg are not reliable due to the

interference of TgAb.

Further Studies

• Emphasize the cost-effectiveness of routine usage of the assay

in clinical practice for TgAb+ve patients.

• Studies of other novel molecular marker such as circulating

brafV600E in the diagnosis and follow-up of DTC

Team Biomarkers welcomes you all to the next chapter –

7th International Conference on Biomarkers & Clinical

Research scheduled for Nov 28-30, 2016 in Baltimore, USA

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Let Us Meet Again in Baltimore, USA